The principal objective of the proposed study is to discover fundamental principles governing the development of the visual system in primates. Work on embryonic and fetal eye and brain directly in nonhuman primates is essential for the understanding of normal and pathological development of the visual system in man. The project consists of three integral parts to be conducted simultaneously: (1) normal prenatal development in rhesus monkey, (2) experimetally perturbed development in the monkey, and (3) correlation of monkey and human development. In the first part, emphasis is on the prenatal mechanisms of neuron genesis, migration, determination and differentiation including axonal growth and synaptogenesis in the retina, subcortical visual centers and visual cortex. In the second part, the consequences of selective destruction of visual centers and/or pathways sustained prenatally will be evaluated in postnatal monkeys to determine the extent of neuronal plasticity and synaptic reorganization. Finally, in order to relate experimental results in nonhuman primates to man, correlative cytological analysis of developmental stages will be made using Golgi and electron microscopic criteria. The experimental analysis is conducted with a battery of modern neurological methods including H3-thymidine autoradiography, Golgi impregnation, electron microscopy, the anterograde and transneuronal autoradiographic and the retrograde transport method for tracing development of neuronal pathways. We have refined a prenatal neurosurgical procedure so that destruction and/or injection of radioactive tracers into selected brain regions during intrauterine life from the 50th day of pregnancy to birth is compatible with survival of fetus. Our pilot studies indicate that the proposed research will yield a new type of data on the development of the primate visual system which may change our concepts and increase our control of human developmental disease.